Revealing the B cell-intrinsic effects of pathogenic KMT2D mutations in Kabuki syndrome (KS) and Cold Agglutinin Disease (CAD)
AIFA Early Career and New Researcher Grant
Dr Etienne Masle-Farquhar
Garvan Institute of Medical Research, Sydney
Research Team: Prof Russell Dale, Dr Melanie Wong, Dr Shruti Swarmy, Dr Jacinta Perram, Dr Katherine Jackson, Prof Susan Clark, Dr Timothy Peters, Christopher Jara, Caitlin Bartie (Garven Institute of Medical Research), Dr Yogesh Jeelall (Sir Charles Gairdner Hospital, Perth)
The goal of this project is to understand how mutations within B lymphocytes, that modify a gene called KMT2D, cause autoimmune disease and/or immune deficiency in young children with Kabuki Syndrome (KS) or in adults with a rare anemia called Cold Agglutinin Disease (CAD). In addition to KS and CAD, mutations in KMT2D are incredibly frequent in up to 30% of B cell non-Hodgkin lymphomas, which are often life-threatening diseases.
By identifying cohorts of patients with these diseases, and using cutting-edge immunology and sequencing methods to identify and study specific “Rogue” B cells harbouring KMT2D mutations, the team hopes to aid in the diagnosis, monitoring and eventually treatment of individuals with KS and CAD. Their findings will also have broad relevance to scientists and clinicians studying or treating B cell lymphomas.