Progressive pulmonary fibrosis (PPF) comprise a heterogeneous group of lung disorders associated with high morbidity and mortality. The MUC5B promoter variant rs35705950 is a common genetic variant associated with great of developing idiopathic pulmonary fibrosis (IPF). As IPF and fibrotic hypersensitivity pneumonitis (fHP) present phenotypic resemblances, we aimed to analyze the role of rs35705950 MUC5B in common molecular pathways linked to PPF.

Herein, taking advantage of our extensive PPF patients? cohort, we found that the frequency of MUC5B rs35705950 GT and TT genotypes was dramatically increased in IPF and fHP, as compared to healthy controls (GT: 57,6% vs. 63,3% vs. 20,7%; TT: 15,3% vs. 10,3% vs. 0,9%).

Furthermore, the distribution of cellular populations in bronchoalveolar lavage (BAL) is comparable between IPF and fHP patients, highlighting the hypothesis that PPF may share common fibroproliferative pathways. Interestingly, when stratifying the fHP patients according to the MUC5B rs35705950 genotype, we observed an increased percentage of macrophages in BAL fluid in individuals carrying the minor allele.

Further studies related to MUC5B protein expression, localization (Fig.1) and function in fHP patients are ongoing. With this approach, we expect to shed light into pathways shared between IPF and fHP, with potential use in early stratification of disease risk and survival.