An international research team co-led by Vanderbilt University Medical Center has identified a new genetic disorder that causes severe immunodeficiency and increased susceptibility to life-threatening infections.
The disorder, which was discovered through genetic sequencing, is caused by a mutation in the gene for the protein IRF4, a key player in the development and function of white blood cells. The study, which was published in the journal Science Immunology, will help identify those who carry the disorder and provide a basis for genetic diagnosis and preventative treatment.
In-born errors of immunity, or primary immunodeficiencies, are genetic defects that lead to increased susceptibility to infectious diseases, autoimmunity, anti-inflammatory disorders, and in some cases, cancer. To date, 485 different types of IEIs have been identified, and it is thought that they occur in 1 in every 1,000 to 5,000 births, making them as prevalent as other genetic disorders such as cystic fibrosis and Duchene’s muscular dystrophy. Despite recent medical advancements, around half of patients with IEIs still lack a genetic diagnosis that could help them avoid debilitating illness and death.
The research team, which includes scientists from The Rockefeller University, the Imagine Institute for the study and treatment of genetic diseases in Paris, and the Monterrey Institute of Technology in Mexico, identified seven patients from six unrelated families across four continents who were suffering from recurrent and serious infections, including pneumonia caused by the fungus Pneumocystis jirovecii. Each patient had the same mutation in the DNA-binding domain of IRF4. Further research using mouse models revealed that the mutation led to a severe deficiency in antibody production and impaired the activation and differentiation of immune cells.
This discovery highlights the importance of genetic research in identifying and understanding rare genetic disorders and the potential for preventative treatment. The researchers, who have formed the IRF4 International Consortium, plan to continue their work to better understand the effects of the mutation and develop treatment options for those affected.