More and more people around the world are suffering because their immune systems can no longer distinguish between healthy cells and invading microorganisms. Instead, the disease defenses that once protected them attack their tissues and organs.
Major international research efforts are underway to combat this trend – including an initiative at the Francis Crick Institute in London, where two world experts, James Lee and Carola Fenosa, have created separate research groups to help identify the exact causes of autoimmune diseases, such conditions are known.
“The numbers of autoimmune cases started increasing about 40 years ago in the West,” he told me. Foreman. However, we are now seeing the emergence of some in countries that did not have such diseases before.
For example, the largest recent increase in IBD cases was in the Middle East and East Asia. Before that they had hardly seen the disease.”
Autoimmune diseases range from type 1 diabetes to rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In each case, the immune system cuts its wires and turns on healthy tissues instead of infectious agents.
In the UK alone, at least 4 million people have developed such conditions, and some individuals have more than one condition. Internationally, it is now estimated that cases of autoimmune diseases are rising by between 3% and 9% annually. Most scientists believe that environmental factors play a major role in this rise.
“Human genes have not changed over the past few decades,” said Lee, who previously worked at Cambridge University. “So something in the outside world has to change in a way that increases our susceptibility to autoimmune disease.”
This idea was supported by Venuesa, who previously worked at the Australian National University. She noted the changes in diet that have occurred as more and more countries adopt Western-style meals and people buy more fast food.
“Fast food meals lack certain important ingredients, such as fiber, and evidence suggests that this change affects a person’s microbiome — the group of microorganisms in our gut that plays a key role in controlling various bodily functions,” he said.
“These changes in our microbiomes then lead to autoimmune diseases, of which more than 100 types have now been discovered.”
The two scientists stressed that individual sensitivities were implicated in the development of such diseases, diseases that also include celiac disease as well as lupus that causes inflammation and swelling and can cause damage to various organs, including the heart.
“If you don’t have a particular genetic susceptibility, you won’t necessarily develop an autoimmune disease, no matter how many Big Macs you take,” Venussa said. “There’s not much we can do to stop the global spread of fast food franchises. So, instead, we’re trying to understand the underlying genetic mechanisms that underpin autoimmune diseases and make some people susceptible but not others. We want to address the problem at this level.”
This task is made possible by the development of technologies that now allow scientists to identify minute DNA differences between large numbers of individuals. In this way, it is possible to identify common genotypes among those with autoimmune diseases.
“Until very recently, we didn’t have the tools to do that, but now we have this amazing power of large-scale DNA sequencing and that has changed everything,” he told me. “When I started doing research, we knew about six different types of DNA were involved in triggering IBD. Now we know more than 250.”
Such work lies at the heart of Lee and Vinuesa’s efforts, which aim to find out how these different genetic pathways work and reveal the many different types of diseases that clinicians are now looking for. “If you look at some autoimmune diseases – for example, lupus – it’s recently become clear that there are many different versions of them, which may be caused by different genetic pathways,” Venuesa said. “It follows when you are trying to find the right treatment.
“We have a lot of potentially useful new therapies that are being developed all the time, but we don’t know which patients to give them to, because we now realize that we don’t know exactly what kind of disease they have. And that is now a major target of autoimmune research. We have to learn how to synthesize patients and stratifying them so that we can give them the appropriate treatment.”
Lee also stressed that the rising incidence of autoimmune diseases worldwide means that new treatments and drugs are more needed than ever. “Currently, there are no treatments for autoimmune diseases, which usually develop in young people – while they are trying to complete their education, get their first job and start families,” he said.
This means that increasing numbers of people will have surgery or will have to have regular injections for the rest of their lives. It can be grim for patients and a tremendous strain on health services. Hence the urgent need to find new and effective treatments.”