Most autoimmune diseases are easy to diagnose but difficult to treat. However, that scenario could change based on the findings of research by Australian, Canadian and North American scientists published in Science. The study proposed using the unique fingerprint of immune cells to quickly identify which treatments will work in case of an autoimmune disease.
“We analyzed the genomic profile of more than one million cells from 1,000 people to identify a fingerprint that links genetic markers to diseases such as multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, spondylitis, inflammatory bowel disease, and Crohn's disease. We were able to do this using single cell sequencing, a new technology that allows us to detect subtle changes in single cells,” explained Joseph Powell, lead author of the paper and researcher at the Garvan Institute for Medical Research in Sydney, Australia.
This discovery could help people find personalized treatments that work for them and guide the development of new drugs. The joint study conducted by researchers in Sydney, Hobart, Melbourne, Brisbane and San Francisco helps to understand why some treatments work well in certain patients, but not others.
It is the largest study to date to link disease-causing genes to specific types of immune cells. A trial is now being conducted in Sydney with patients with Crohn's disease that attempts to anticipate which treatments will work for specific patients.
“Some autoimmune diseases can be notoriously difficult to treat,” Powell said. Because of the complexity of our immune system and how much it varies between individuals, we currently don't have a good understanding of why a treatment works well in some people but not in others.”
The study linked specific genes and types of immune cells to a person's disease. This means that an individual's unique genetic profile could be used to administer treatments tailored to precisely tame their immune system.
“Our data also provides a new avenue to reduce potential drug targets. The potential health and economic impacts of this research are enormous,” explained Alex Hewitt, joint lead author and clinical researcher at the Menzies Institute for Medical Research at the University of Tasmania. Most rare genetic diseases are like a big car accident in the body: they are usually easy to identify and locate in the genome where they occur. But immune diseases often look more like traffic congestion, where genetic changes that stop it are more difficult to identify specifically. This study has helped us to identify pain points.”
Immune systems are designed to combat external threats, but autoimmune diseases occur when the immune system targets healthy cells themselves. These are ailments that affect one in 12 people in the world and require lifelong treatments to minimize harm. Often, over the course of the illness, patients will try many different treatments before finding one that works for them.
“Some drugs can be very effective in only 15% of patients, so they are not recommended as a first-line treatment,” says Seyhan Yazar, co-author of the study. We now have a way to link the response to treatment with an individual's immune genetics, and potentially detect that 15% of patients before a doctor even administers treatment.”
Researchers say their data could reduce the risks associated with developing new treatments. “Pharmaceutical companies can have hundreds of goals and must make decisions about which ones will lead to Phase I clinical trials, knowing that 90% of potential drug candidates fail during clinical development,” said José Alquicira-Hernández, lead co-author and researcher at the Garvan Institute. Understanding what types of cells are relevant to a particular disease is key to developing new drugs.”
The study provides unique information by looking at genes in individual immune cells on an unprecedented scale. It analyzed the genomics of more than one million individual immune cells from around 1000 healthy individuals, exploring 14 different types of immune cells in total.
This individual approach constructs a much clearer picture than previous studies that analyzed combined cells in a blood sample. “The problem with bulk RNA analysis is that we only look at one averaged signal. But there is great variation in cell functions and the types of cells that allow the body to defend itself against attacks,” Yazar explains. The average analysis does not reflect what happens in the full variety of immune cells.”
“We are working on a study of Crohn's disease in collaboration with St. George who will determine how a patient's immune genotype affects their response to different treatments and we seek to establish new trials in a variety of autoimmune diseases,” Powell concluded. It is a significant milestone that aims to show how genetics contribute to the risk of immune diseases at the cellular level.”
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