Chronic hypersensitivity pneumonitis is a long-term lung condition in which the interstitial tissue surrounding the alveoli of the lungs becomes inflamed and develops fibrosis.
Investigators have discovered a link between chronic hypersensitivity pneumonitis (CHP) and a variation in the TOLLIP gene, according to a study published in Chest. This gene encodes the toll-interacting protein (TOLLIP), which acts as a negative regulator of innate immunity.
CHP is a long-term lung condition in which the interstitial tissue surrounding the alveoli of the lungs becomes inflamed and develops fibrosis, which occurs when susceptible individuals inhale allergens. The mechanics behind the development of the condition are currently unknown. The investigators examined a cohort of patients with CHP and analyzed genetic variation in single-nucleotide polymorphisms (SNPs)—places in the genome where variation occurs at a single position in the DNA sequence.
“We found that one genotype of an SNP known as rs5743899 was associated with a higher degree of immune activation and an increase in the cellular signaling responses leading to fibrosis,” said Shinji Katayanagi, lead author of the study, in a press release. “This causes a progressive reduction in lung function in patients with CHP.”
According to the investigators, patients with the “GG” genotype of this SNP showed more severe disease progression and a steeper decline in the forced vital capacity (FVC), a test of lung function that measures the maximum amount of air able to be expelled from the lungs after a maximum inhalation. These patients had lower levels of TOLLIP in the lungs compared with patients with the other genotypes and showed increased fibrotic activity in the lungs. Further, the investigators identified a higher level of the phosphorylated form of a protein called Smad2, a major component of the fibrotic pathway, and increased levels of periostin, a marker of fibrosis.
“It seems that the functional changes caused by the TOLLIP variant are associated with rapid FVC decline in CHP due to the dysregulation of fibrosis-related signaling pathways such as Smad/TGF-β and NF-κB signaling,” said Yasunari Miyazaki, senior author of the study, in the release.
The investigators believe that the association between this genotype of the rs5743899 SNP and a poorer prognosis of CHP could be invaluable in the assessment of patients at their initial diagnosis and could potentially help guide their treatment.
Genetic variant linked to prognosis of chronic hypersensitivity pneumonitis [news release]. EurekAlert; November 16, 2021. Accessed November 29, 2021. https://www.eurekalert.org/news-releases/935039