Genetic Mutation Linked To Rare Lung Conditions: Study

Published in Cell, this discovery marks the first association between the missing CCR2 receptor and the disease

Researchers from Rockefeller University, in collaboration with other institutions, have identified a previously unknown hereditary illness that leads to defective cell function. The breakthrough came when observing a distinct subset of children who battled life-threatening conditions such as progressive polycystic lung disease, pulmonary alveolar proteinosis (PAP), and recurring respiratory infections.

The genomic data of these children revealed a common characteristic—the absence of a chemical receptor known as CCR2, essential for activating alveolar macrophages in the lungs. Published in Cell, this discovery marks the first association between the missing receptor and disease.

The study disclosed that these children were not only lacking CCR2 but also had only half the normal counts of pulmonary alveolar macrophages. These macrophages, responsible for combating infections and maintaining surfactant levels in the lungs, were found to be crucial for proper lung defence.

Dr Jean-Laurent Casanova from Rockefeller University expressed surprise at the essential role CCR2 plays in alveolar macrophage function, stating that individuals without it operate at a disadvantage in lung defence and cleanup.

The investigation initially focused on two Algerian sisters with severe PAP but lacked the typical autoantibodies associated with the condition. Instead, they had a genetic mutation leading to the absence of CCR2. Further analysis identified seven more children with the same CCR2 mutation and serious lung conditions from the United States and Iran.

The findings revealed that the genetic variant resulted in reduced pulmonary alveolar macrophages, leading to compromised lung tissue cleanup and increased susceptibility to mycobacterial infections. Live-imaging analysis demonstrated that monocytes lacking CCR2 signaling wandered, highlighting the importance of the receptor in directing immune cells to infection sites.

The study also explored the consequences of the deficiency on vaccination outcomes, revealing challenges in assembling macrophages at vaccination sites, leading to infections and tissue destruction.

The children inherited the deficiency from their parents, who remained healthy carriers of one disease copy of the gene. Consanguineous marriages, where parents are related, were identified as a contributing factor to the higher risk of inheriting the CCR2 mutation.

This groundbreaking research sheds light on a previously unrecognised genetic link to severe lung conditions, paving the way for further understanding and potential treatments.



Around The World