APR 15, 2022 9:33 AM PDT

Immune Cell Fingerprints Can Help Reveal New Autoimmune Disease Treatments

WRITTEN BY: Carmen Leitch

The immune system is an incredibly complex system that has to be able to rapidly spring into action, and then shut down when the job is complete. Cells on the front lines of the immune system must recognize dangerous invaders and attack them, while leaving our own cells and tissues alone. When there are disruptions in these processes, autoimmune disease can arise. Those conditions are difficult to treat. Researchers may have made some progress on that front, however, by creating a new approach that assesses the 'fingerprint' of immune cells to find the best way to treat autoimmune disorders.

Image credit: Pixabay

In a new study reported in Science, researchers used single-cell sequencing to generate a genomic profile for over one million cells that were taken from nearly 1,000 individuals. The data was used to create a fingerprint that linked "genetic markers to diseases such as multiple sclerosis, rheumatoid arthritis, lupus, type 1 diabetes, spondylitis, inflammatory bowel disease, and Crohn's disease," explained co-lead study author Professor Joseph Powell of the Garvan Institute of Medical Research.

The research connected specific types of immune cells and genes they express to certain autoimmune diseases. This work is getting us closer to using a patient's genomic data or genetic profile to tailor a personalized course of treatment. The researchers are hopeful that this study will open up new treatment options by revealing drug targets, and help explain why some therapies work well in some patients and not at all in others.

Many rare genetic diseases can be traced by to a specific error in the genome and can be easy to identify because the connection is clearly defined. But immune diseases are more complicated, and are not necessarily due to a single genetic problem. This study can help reveal what genes and what types of cells are involved in autoimmune diseases. Then, rather than creating a ton of different compounds and testing them all to see which ones have some effect on various parts of the immune system, researchers can use data from this study to pinpoint which cells in particular they should focus on, and the genes that are active in those cells, to create 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 percent of potential drug candidates fail during clinical development," noted co-first study author Dr. José Alquicira-Hernández, a researcher at the Garvan Institute. "Understanding which cell types are relevant for a particular disease is key for developing new drugs."

Instead of analyzing all of the genes that were expressed in many types of cells in the blood in a kind of bulk analysis, this research focused on the peripheral blood mononuclear cells (PMBCs), fourteen types of immune cells including monocytes and macrophages, from the nearly 1,000 samples taken from healthy individuals. Single-cell RNA sequencing was performed to see how differences in genes affected the immune system at the cellular level. Genetic changes were found to influence the expression of proteins that help control the immune system and are involved in immune pathways.

This research can help us understand how the immune system is regulated in healthy individuals, and what goes wrong in those with autoimmune disease. A clinical trial is now underway, assessing how the genomes of Crohn's disease patients influences their response to treatments.

Sources:  Garvan Institute of Medical Research, Science

About the Author
BS
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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