Professor Stuart Tangye, a speaker at the RCPA’s annual conference earlier this month, explains how next generation sequencing (NGS) for the diagnosis of primary immunodeficiencies (PID) is providing increased opportunities for precision or personalised medicine. This comes following the recent discovery of many new gene defects, with implications for many patients.

Prof Tangye explains that new breakthroughs in genetic technologies are helping to detect previously unknown gene defects, providing more treatment options for patients.

“The implications of new cutting-edge genetic technologies are huge for patients. Whole genome sequencing (WGS) is becoming much more available globally and is now not just restricted to top end research or diagnostic facilities – it is available in many centres across Australia. These breakthroughs in genetics allow us to not only treat the symptoms, but also enables us to treat the root cause of the disease. This has really expedited improved diagnosis rates and patient management for many more families or individuals.

“By using whole genome sequencing (WGS), we are getting a much better rate of diagnosis in individuals with PID, the implications of which then extend to the family including siblings or carriers of the same genetic defect. The real game changer is that we are able to detect the specific disease-causing gene defect which will then determine treatment options. This is proving to be extremely empowering to the clinicians, the families, the patients and also provided the research opportunities that have come from these discoveries,” said Prof Tangye.

Primary immunodeficiency disorders (PID) are a set of syndromes that arise from genetic defects that affect the development and function of the immune system. Most are diagnosed in young children, and patients are generally characterised by increased susceptibility to infections. However, affected patients can also be susceptible to developing other clinical features including autoimmunity, allergy and even cancer.

Although the most severe forms of PID are identified in early childhood, many patients present in adulthood, typically with no apparent family history and a variable clinical phenotype of widespread immune dysregulation: about 25% of patients have autoimmune disease; allergy is also prevalent and up to 10% develop lymphoid malignancies.

“These disorders are not as rare as we think. When viewed as a collective, they are more common than some of the diseases that are already known, such as some of the more well-known cancers. Through ongoing genetic research, we are able to define the genetic cause of a particular syndrome that previously was undocumented. Previously, when people with these diseases were being cared for, we just didn’t know why these people were sick. Now we have a genetic handle on that which helps to reveal the mechanisms of the disease and can help to implement better patient management.

“These advances have been enabled by the accessibility and affordability of very advanced genetic technologies. Thanks to these advances we are always making these new discoveries. A WGS approach in the diagnosis of PID can increase diagnostic yield and further our understanding of the key pathways that influence immune responsiveness in humans,” said Prof Tangye.