A novel genetic cause of inborn error of immunity – validation and therapeutics

AIFA Early Career Researcher Grant 2023

Chief Investigator: Dr Shruti Swamy, Garvan Institute of Medical Research, Sydney      

Research Team: A/Prof Elissa Deenick, Prof Tri Phan and Mr Aidan Telfsar (Garvan Institute), Dr Peter Hsu (The Children’s Hospital at Westmead) 

Inborn errors of immunity are genetic conditions that cause those affected to have a dysfunctional immune system. This can lead to problems such as susceptibility to infection, allergy and autoimmunity.

The team at the Garvan Institute of Medical Research identified two siblings both of whom developed severe lung disease at a very early age (under 3 years old). They suspected that these two siblings had a genetic cause of their disease, so undertook genetic testing and examined their whole genome. This identified part of one gene that was missing in both patients suggesting that the lack of this gene was causing the disease in these patients. Lack of this gene has never been described as causing disease before, making this a novel finding. To improve treatment of these patients the researchers need to understand how this gene affects immune cells and causes their lung disease.

To investigate this further the team used genetic engineering to make a mouse “avatar” which had the same genetic change as the patients. Using these mice, as well as lung and blood cells from the patients, they will investigate what changes this genetic deletion causes. They will also use the mouse avatars to test whether bone marrow transplant might restore proper immune function and stop the lung damage.

This project will provide important information to provide a diagnosis for these patients and their family and identify potential treatments.  It will further add to the genetic database of known genes implicated in inborn errors of immunity.