A recent study published in the Journal of Allergy and Clinical Immunology by scientists from deCODE genetics, a subsidiary of Amgen, has identified a rare missense variant in the STAT6 gene that appears to confer protection against asthma.
Asthma is a complex, chronic inflammatory disease of the airways, affecting approximately 300 million people globally. Among asthma patients, an estimated 5-10% suffer from severe, steroid-resistant forms of the condition. The newly identified missense variant results in lower levels of the STAT6 protein in activated T-cells, leading to a diminished T2-mediated response from several downstream genes. This alteration reduces the cells’ ability to initiate and sustain T2 inflammatory responses.
The study highlights that individuals carrying this variant are 73% less likely to develop moderately severe to severe T2-high asthma compared to non-carriers. Additionally, the variant is associated with significant reductions in other T2-related molecules and cell types, including immunoglobulin E (IgE), eosinophils, and basophils.
However, the missense variant is extremely rare outside of Iceland, complicating direct replication of these findings in other populations. Despite this, a similar protective effect against asthma and lower eosinophil counts was observed in burden tests conducted in Iceland, Denmark, and the UK, which analyzed all rare variants predicted to have loss-of-function or deleterious effects on STAT6.
Conclusion
The STAT6 pathway is a key target for asthma biologics, with current treatments focusing on specific molecules within the T2 inflammatory response. Downregulating STAT6 in clinical settings may enhance the therapeutic effects of these biologics, making it a promising target for the development of new treatments for severe, uncontrolled T2-high asthma.
Related Topics:
-
Research Reveals The Influence Of Parents On Children’S Brain Development And Mental Health
-
Digital Avatars Can Alleviate The Pain Caused By Disturbing Voices In Psychiatric Patients
