An immune `fingerprint' reveals path for better treatment of autoimmune diseases
Date:
April 7, 2022
Source:
Garvan Institute of Medical Research
Summary:
Most autoimmune diseases are easy to diagnose but hard to treat. A
new article proposes using your unique immune cell fingerprint to
rapidly identify which treatments will work for your autoimmune
disease.
FULL STORY ==========================================================================
'We analysed the genomic profile of over one million cells from 1,000
people to identify a fingerprint linking genetic markers to diseases such
as multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, spondylitis, inflammatory bowel disease, and Crohn's disease,' says
Professor Joseph Powell, joint lead author at the Garvan Institute of
Medical Research. 'We were able to do this using single cell sequencing,
a new technology that allows us to detect subtle changes in individual
cells,' he says.
==========================================================================
The discovery could help individuals find tailored treatments that work
for them and guide the development of new drugs.
The study by researchers in Sydney, Hobart, Melbourne, Brisbane and San Francisco helps us understand why some treatments work well in some
patients, but not in others. It's the largest study to date to link disease-causing genes to specific types of immune cells.
A trial is now underway in Sydney with Crohn's disease patients to
predict which treatments will work for specific patients.
'Some autoimmune diseases can be notoriously difficult to treat,' says Professor Powell.
'Because of our immune system's complexity, and how vastly it varies
between individuals, we don't currently have a good understanding of
why a treatment works well in some people but not in others,' he says.
==========================================================================
The study links specific genes and immune cell types to an individual's disease, including multiple sclerosis, rheumatoid arthritis, inflammatory
bowel disease, type 1 diabetes and Crohn's disease.
This means an individual's unique genetic profile could be used to
deliver treatments tailored to precisely tame their immune system.
'Our data also provides a new avenue for narrowing down potential drug
targets.
The potential health and economic impacts of this research are enormous,'
says Professor Alex Hewitt, joint lead author and clinician-researcher
at the University Of Tasmania's Menzies Institute for Medical Research.
'Most rare genetic diseases are like a major car accident in the body --
they are generally easy to identify and locate where they occur in the
genome. But immune diseases are often more like traffic congestion,
where genetic changes that hold up traffic are harder to specifically
pinpoint. This study has helped us identify the trouble spots,' says
Professor Hewitt.
'The greatest insight from this work will be identification of therapeutic targets and defining sub-populations of immune disease, which can then
refine clinical trials to assess drug effectiveness,' he says.
==========================================================================
Our bodies' immune systems are designed to fight external threats, but autoimmune diseases occur when our immune systems take aim at our own
healthy cells. They affect about one in 12 Australians, are incurable
and require lifelong treatments to minimise the damage.
Often, patients will trial many different treatments before finding one
that works for them.
'Some medications may be very effective in only 15% of patients, so
are not recommended as a first-line treatment,' says Dr Seyhan Yazar,
co-first author of the study.
'We now have a way to link treatment response back to an individual's
immune genetics -- and to potentially screen for that 15% of patients
before a clinician even administers a treatment.' The researchers
say their data could lower the risks associated with developing new
treatments.
'Pharmaceutical companies may have hundreds of targets and have to make decisions about which they will take forward to Phase I clinical trials, knowing that 90% of potential drug candidates fail during clinical development,' says Dr Jose' Alquicira-Herna'ndez, co-first author and researcher at the Garvan Institute.
'Understanding which cell types are relevant for a particular disease
is key for developing new drugs.' A million cells reveal complexity and provide certainty The study provides unique insights by looking at genes
in individual immune cells on an unprecedented scale. It analysed the
genomics of more than one million individual immune cells from around
1,000 healthy individuals, exploring 14 different types of immune cells
in total.
This individual approach paints a far clearer picture than previous
studies which analysed combined cells in a blood sample.
'The problems with bulk RNA analysis is that we only observe an averaged signal. But there is vast variation in cell functions and cell types
that allow the body to defend against attack,' explains says Dr Yazar.
'Average analysis doesn't reflect what happens in the full variety of
immune cells.' Integrating into clinical trials The findings have led
to clinical trials.
'We are working on a study of Crohn's disease in collaboration with St
George Hospital that will determine how a patient's immune genotype
affects their response to different treatments and are looking to
establish new trials in a range of autoimmune diseases' says Professor
Powell.
'It is a significant milestone of Garvan's pioneering OneK1K study aimed
at showing how genetics contribute to the risk of immune disease at a
cellular level.'
========================================================================== Story Source: Materials provided by
Garvan_Institute_of_Medical_Research. Note: Content may be edited for
style and length.
========================================================================== Journal Reference:
1. Seyhan Yazar, Jose Alquicira-Hernandez, Kristof Wing, Anne
Senabouth, M.
Grace Gordon, Stacey Andersen, Qinyi Lu, Antonia Rowson, Thomas
R. P.
Taylor, Linda Clarke, Katia Maccora, Christine Chen, Anthony
L. Cook, Chun Jimmie Ye, Kirsten A. Fairfax, Alex W. Hewitt,
Joseph E. Powell.
Single-cell eQTL mapping identifies cell type-specific genetic
control of autoimmune disease. Science, 2022; 376 (6589) DOI:
10.1126/ science.abf3041 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220407141954.htm
--- up 5 weeks, 3 days, 10 hours, 50 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)