Published Online: August 31, 2016
Primary immunodeficiency diseases (PIDDs) are conditions caused by abnormalities of the immune system that can be passed from one generation to another. In the past, attempts to identify the genetic causes of PIDDs were both time- and resource-consuming. Modern technology has advanced to allow these studies to be performed more rapidly and extensively. It still had not been determined, however, whether the methods would be useful for the management of patients with PIDDs.
In a large collaborative research study recently published in The Journal of Allergy and Clinical Immunology (JACI), Stray-Pedersen and colleagues presented nearly 280 families with PIDDs and no known genetic cause from 22 countries. These families were recruited in an unbiased manner that offered participation and enrolled subjects with primary immunodeficiency diseases of any type. The participants underwent whole exome sequencing, which is a technology that focuses upon DNA sequencing of all protein-encoding genes in an individual. The study subjects were also tested for copy number variations, such as large duplications or deletions, in their genes.
Using these new genetic technologies, the investigators were able to identify confirmed or likely explanations for 40% of the families. This approach enabled the researchers to detect key changes not only in established PIDD-causing genes, but also in genes that cause other diseases as well as novel genes not previously known to cause human disease. Furthermore, one of out every 9 families that had one genetic finding had a second genetic mutation contributing to the individual’s disease presentation. Discovery of these alternative genetic defects would have been more difficult using older technologies. Importantly, the identification of the genetic abnormality directly impacted clinical management in 25% of the affected individuals.
In this first report of a large, unbiased population of families with PIDDs from around the world, researchers were able to demonstrate the utility of these new genomic approaches for diagnosis and management of otherwise difficult to diagnose patients with PIDDs. As these genomic tests have become widely available, medical providers might want to consider using these tests as part of their evaluation of patients with PIDDs.
The Journal of Allergy and Clinical Immunology (JACI) is an official journal of the AAAAI.