Primary immunodeficiencies (PIDs) were initially defined as rare genetic disorders affecting the development or function of the immune system. However, it has become apparent in recent years that PIDs are much more common than initially thought. It has even been suggested that a high percentage of patients with severe infections since childhood have inborn errors of immunity. Greater awareness and better collaboration in recent years have led to the clinical definition of at least 300 PIDs. Most PIDs are monogenic diseases, and up to 200 genes have been implicated in these conditions. Individuals with PIDs typically present severe or recurrent infections, often with autoimmunity, and, occasionally, with allergy and cancer.

Despite recent advances, the genetic basis of a significant proportion of PIDs remains undefined. High-throughput sequencing techniques are potent tools that should make it possible to develop precision medicine for patients with unknown gene defects. However, these techniques are not routinely available in clinical immunology units. Only collaborative projects, in which research laboratories work with clinical

Immunology units can make such precision medicine available to patients who do not yet have a genetic diagnosis.

The objective of this research line is to find new genetic etiologies in patients with PIDs, using whole exome sequencing. Upon identification of a positive genetic hit, we will follow up with an exhaustive characterization of the gene responsible for the pathology and decipher its role in the immune system. The project lies within the framework of precision medicine, to herald a rapid acceleration of genetic diagnosis in PIDs, allowing for genetic counseling to the families, and defining the best therapeutic options for patients to improve their treatment management and outcome.

LIGHD has extensive experience in the discovery of new genetic etiologies of PIDs.

The main challenge in the study of PIDs is that each patient is unique. The causal gene must therefore be investigated individually, to determine the best therapeutic option.