Why Me? The Diabetes – Genes Autoimmunity and Prevention Study may help find the answer.
The Diabetes Genes, Autoimmunity and Prevention (D-GAP) study, led by Professor Mark Peakman looked to uncover the connections between genes, the body’s immune response and Type 1 diabetes. Specifically, they tried to establish if some of the genes linked to Type 1 diabetes directly affect our ‘immune phenotype’ – the characteristics of our bodies’ immune systems. By confirming this link, the causative immune phenotypes in Type 1 diabetes would be identified. In turn these could become the targets for drug development, or specific blood markers for measuring success in clinical trials testing new methods for treating or even preventing Type 1 diabetes.
Each cell in your body contains chromosomes. Chromosomes are made up of a catalogue of genes – sections of DNA that act as a ’recipe books’ with instructions for how to make all of machinery a cell needs to fulfil it’s role in the body. The particular selection of gene recipes we inherit from our parents determines our biological make up. For example, there are six genes which contribute to determining your eye colour and different ‘flavours’ or natural variations in these genes influence whether you have blue eyes or brown eyes.
In the D-GAP study, researchers are examining how different flavours of genes associated with type 1 diabetes can make you more or less susceptible to developing Type 1 diabetes.
The D-GAP team asked brothers and sisters of young people with Type 1 diabetes, diagnosed before the age of 16 to take part in the study. These brothers and sisters share much of the same genetic ‘recipe book’ as the young person with Type 1 diabetes. It’s therefore likely that some of the siblings, although they do not have diabetes, would have the genes which could predispose them to the condition.
Immunity is how our bodies learn to protect us from harmful attack – for example from parasites or viruses. Our bodies develop immunity both passively (passed on from mother) or actively (through exposure or inoculation). Autoimmunity is where the body mistakenly identifies part of itself as being harmful, leading to the body to launch an immune attack against its own tissues. In Type 1 diabetes, that autoimmune reaction is directed at the insulin producing beta cells of the pancreas.
T cells are a group of white blood cells that play a central role in immunity. Through receptor molecules on their surfaces, T cells directly attack cells and particles that they identify as ‘foreign’ or harmful. To do this, they bind to the ‘foreign’ particle and trigger a reaction to destroy them and remove them from the body. There are many millions of T cells in our bodies, with a huge variety of receptors. This enables our bodies to respond quickly and efficiently to virtually any foreign body.
There are two very important types of T cells that have a key role in type 1 diabetes. Autoreactive T cells are cells that recognise and attack the beta cells in the pancreas. Regulatory T cells exist to control this over zealous response. The D-GAP study attempted to track down and study the autoreactive T cells that attack the beta cells, by measuring the levels of these ‘bad’ T cells in both people without diabetes, and in people who have just been diagnosed with the condition.
The D-GAP researchers identified variations in immune response by comparing DNA samples from those with and without Type 1 diabetes by measuring the levels of regulatory and autoreactive T cells in people newly diagnosed.
The D-GAP study only examined the genetic aspect of developing Type 1 diabetes and therefore examined only one part of the puzzle about what triggers the development of Type 1 diabetes. While we know that genetic predisposition is a vital part of this equation, we also know that something else, a so-called ‘environmental factor’, is also necessary. Even though much other research around the world is focusing on finding out what this factor might be, scientists have as yet been unable to identify it – which probably means there is a complex combination of factors at play.
The study showed that there are probably different types of immune response in patients with Type 1. These different types may require different kinds of therapeutic approach i.e. personalised medicine – the right drug for the right person at the right time. Based on the work in DCAP it is believed that vaccines may be even more effectiv3e in some people than in others. These findings have been very useful to inform the MonoPepT1De clinical study.