Genetic Disease Causes Recurrent Respiratory Infections

A rare genetic disease has been discovered which predisposes patients to severe respiratory infections and lung damage.

The genetic mutation identified affects the immune system, and physicians are hopeful that new drugs that are currently undergoing clinical trials to treat leukemia may also be effective in helping individuals with this debilitating disease.


International collaborating scientists led by those at the University of Cambridge (Cambridge, UK) examined genetic information from individuals who suffer from immunodeficiency and are predisposed to infections. From this group, they identified a unique genetic mutation in 17 patients that suffer from severe respiratory infections and rapidly develop lung damage.

DNA samples were isolated from blood or peripheral blood mononuclear cells (PBMCs). Exome target enrichment was carried out using either the SureSelect kit (Agilent; Santa Clara, CA, USA) or the Truseq kit (Illumina; San Diego, CA, USA). The lipid kinase activity was determined using a modified membrane capture assay and many other complementary assays were also performed.

The team found that the genetic mutation increases activity of an enzyme called Phosphoinositide 3-Kinase δ (PI3Kδ). The enzyme is present in immune cells and regulates their function. However, constantly activated PI3Kδ impairs work of these immune cells, preventing them from responding efficiently to infection and providing long-lasting protection. Consequently, patients with this mutation have severe and recurrent infections.

Sergey Nejentsev, MD, PhD, a Wellcome Trust Senior Research Fellow from the University of Cambridge who led the study said, “We called this newly identified disease Activated PI3K-δ Syndrome (APDS) after the enzyme in the immune system that is affected by the genetic mutation. It is very important that doctors consider a possibility of APDS in their patients. A simple genetic test can tell if the patient has the mutation or not. We believe that now many more APDS patients will be identified all over the world.” The study was published on October 17, 2013, in the journal Science Express.

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