'Assassin' cells play key role in deadly drug reactions
A common pathogenic population of locally proliferating cytotoxic CD8+ LAG3+ TRM T cells with private expanded and unexpanded TCRαβ clonotypes drives keratinocyte-specific cell death across patients with diverse HLA-restricted drug-induced SJS/TEN. Credit: Nature Communications (2024). DOI: 10.1038/s41467-024-52990-3

Researchers have identified the skin cells responsible for orchestrating cases of two of the most life-threatening drug reactions. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) cause the skin and mucous membranes to blister and detach, and carry an average mortality rate of 20%.

In a study published in Nature Communications, researchers reveal that cytotoxic CD8+ T-cells, which are activated and armed within the skin itself, target and kill the very skin cells (keratinocytes) that enable their activation.

For the first time, advanced single-cell multi-omic sequencing techniques were used to analyze the skin and blister fluid of SJS/TEN patients, and this approach identified previously unknown cellular and molecular signatures and interactions between immune cells and skin cells that drive the destructive process.

Professor Elizabeth Phillips MD, Director of the Center for Clinical Pharmacology at Murdoch University’s Institute for Immunology and Infectious Diseases (iiid), said the findings could lead to tools for both earlier diagnosis and more targeted and effective treatments for sufferers of SJS/TEN.

“One of the most intriguing findings of the study is that the skin or epidermal cells known as keratinocytes play a key role in arming the T cells. Keratinocytes not only activate the CD8+ T-cell assassins, but they also seem to lose some of their natural defenses,” Professor Phillips said.

“This creates a self-destructive cycle where the very cells responsible for protecting the skin are turning the immune system against themselves.”

Although these CD8+ T cells only expand in the skin after exposure to the triggering drug, Professor Phillips said that previous work from this research group demonstrated that for certain drugs, HLA typing can be used preventively to identify individuals at risk of developing SJS/TEN by avoiding their exposure to the drug.

“This is a major step forward in understanding and combating rare but severe drug reactions, bringing hope to patients and families affected by these devastating conditions,” Professor Phillips said.

More information:
Andrew Gibson et al, Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis, Nature Communications (2024). DOI: 10.1038/s41467-024-52990-3

Provided by
Murdoch University


Citation:
‘Assassin’ cells found to play a key role in deadly drug reactions (2024, October 28)
retrieved 28 October 2024
from https://medicalxpress.com/news/2024-10-assassin-cells-play-key-role.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.





Source link

Leave a Reply

Your email address will not be published. Required fields are marked *

Before you post, please prove you are sentient.

what is 6 plus 6?

Explore More

Patients Are Relying on Lyft, Uber To Travel Far Distances to Medical Care

When Lyft driver Tramaine Carr transports seniors and sick patients to hospitals in Atlanta, she feels like both a friend and a social worker. “When the ride is an hour

Preventive care is free by law, but many Americans get incorrectly billed − especially if you’re poor, a person of color or don’t have a college degree

Even though preventive care is supposed to be free by law for millions of Americans thanks to the Affordable Care Act, many don’t receive recommended preventive services, especially racial and

Rare cancer could be caught early using simple blood tests

A pioneering study into myeloma, a rare cancer, could lead to GPs using simple blood tests to improve early diagnosis. The study investigated the best combination of blood tests that