A Gene Mutation Linked to Respiratory Infection and Airway Damage

Respiratory infections are known to be the most common illness experienced by individuals worldwide.  It has been shown that repeated respiratory infections can lead to a condition known as “bronchiectasis” that results from a dilation of the bronchi – specialized tubes that carry air from the trachea to the lungs.  Susceptibility to repeated respiratory infections and the resulting bronchiectasis may be due to an underlying primary immunodeficiency (PID).

There have been over 200 genes implicated in PIDs.  This expanded understanding of the role of genetic mutations in regards to susceptibility to respiratory infections among the world’s human population, is due in large part to the application of the advances made in genetic engineering and the fact that the human genome has been entirely deciphered.

To further elucidate the molecular biology of PID, Dr. Ivan Angulo and his colleagues in the Department of Medicine at the University of Cambridge, Cambridge UK, searched for the presence of genetic mutation(s) that might account for PIDs in thirty-five patients suffering from this syndrome.  These patients all suffered from repeated respiratory infections and a family history of susceptibility to these infections.   The fact that a family history was demonstrated, reinforced the assumption of a genetic predisposition.

In regards to the patients studied, the investigators were able to implicate a mutation in the PIK3CD gene that is responsible for the production of the catalytic subunit for the phosphoinositide 3-kinase δ enzyme.  The PID associated with this particular mutation is referred to as the activated PI3K- δ syndrome (APDS).  

An obvious question follows from these results as to the nature of the relationship between the phosphoinositide 3-kinase δ enzyme and the resulting disease state.  The investigators were able to show that the patient-derived immune-competent lymphocytes responsible for combating infection were prone to premature cell death, thereby increasing the likelihood of respiratory distress.  The application of these findings could eventually lead to therapeutic approaches to combat APDS.