Introduction: Up to 40% of patients with hypersensitivity pneumonitis (HP) progress to pulmonary fibrosis, suffering a loss of lung function that can lead to death. The aim of this study was to determine the involvement of the immune response in the development of pulmonary fibrosis in patients with advanced HP.

Methods: Cross-sectional study conducted in 19 patients with fibrotic HP and 10 patients with idiopathic pulmonary fibrosis (IPF) who underwent lung transplantation. Healthy donors (n = 8) were included as control group. Lung samples were obtained from Vall d?Hebron and Ciberes Biobanks. Cytokines with a Th1, Th2 and Th17 profile were determined in tissue homogenate supernatant and MUC16, biomarker of fibrosis progression, was analysed in paraffin-embedded lung tissue.

Results: Both patients with fibrotic HP and IPF had higher levels of GM-CSF, IL-7, IL-13 and IL-23 compared to healthy donors. Fifty per cent of patients with fibrotic HP had a more pronounced Th2 profile with higher levels of IL-5 and IL-6. This group of patients also had increased levels of IL-1?, IL-8, G-CSF and MCP-1 compared to HP patients with a low Th2 profile. HP patients with an increased Th2 profile had higher levels of IL-7 and IL-17 while those with a low Th2 profile had higher levels of IL-2, IL-12 and IL-23 compared to healthy controls. Maximum expression of MUC16 was observed in patients with IPF.

Conclusions: Both patients with fibrotic HP and IPF have increased levels of Th17-related cytokines. HP patients with a high Th2 profile have an increased activation of the adaptive immune response with high production of cytokines involved in the recruitment of granulocytes.

Study funded by ISCII(PI18/00345), FEDER and FUCAP.