A variant in the TYK2 gene, which encodes an immune system protein, may work to protect people from autoimmune disorders, including multiple sclerosis (MS), without overly depressing the body’s ability to fight opportunistic infections, researchers at the University of Oxford report.
Their study, “Resolving TYK2 Locus Genotype-To-Phenotype Differences In Autoimmunity,” was published in the journal Science Translational Medicine.
Autoimmune diseases are characterized by overly active cells of the immune system, which react against the body. For that reason, current treatments for MS and other autoimmune disorders include effects that weaken the immune system, but these therapies leave patients vulnerable to infections and other illnesses.
To understand which molecular mechanisms could help balance immune system activity, researchers investigated genetic variants, influencing the function of a gene called TYK2.
The protein produced by this gene (with the same name) plays a crucial role in maintaining a person’s immunity, as it contributes to fighting off infections or cancer. However, this protein can also promote the development of autoimmune disorders.
Importantly, researchers found that a single variation in the TYK2 gene led to reduced production of the protein — to levels that were no longer able to trigger autoimmune disorders, but were just enough to still protect a person against other diseases. These results indicate that treatments that promote optimal production levels of TYK2 may be effective and safe options for patients with autoimmune disorders.
“Developing new drugs is a costly and time-consuming process,” said Lars Fugger, the study’s senior author, in a news release. “On average it costs over £1 billion and takes over 10 years to bring a new drug to market, and more than 90% of drugs that enter into clinical trials are not ultimately approved. This is because the majority of drugs fail to demonstrate sufficient efficacy to treat disease or they are associated with severe unwanted side effects.”
“While our research indicates that TYK2 could be a good drug target for treating autoimmune diseases, drugs that block the activity of immune cells have been known to leave patients vulnerable to infections and to increase the risk of cancer,” he added. “However, by interrogating data available through the UK Biobank, the most comprehensive health study in the UK, we found that people carrying the protective TYK2 genetic variant were no more likely to have serious infections or to develop cancer than people without the variant.”