Abstract

Background

We hypothesized that the type and magnitude of the lung immune response may relate to specific pathological features in Idiopathic Pulmonary Fibrosis (IPF). 

Methods

In IPF lungs, we characterized the lung immune response applying immune deconvolution methods (GSVA) to transcriptomic data (n=109). Main results were validated in two independent sets of IPF samples: n=26 from the University of Pittsburgh and n=13 from the CIBERES biobank.

Results

IPF lung samples were split in two clusters, differing in the type and level of immune infiltration. Being mostly different in cytotoxic (0.29 vs. -0.38, p=2.68·10-18) and B cell (0.19 vs. -0.26, p=2.08·10-9) levels. These observations were reproduced in two independent sets of IPF samples using different methods: (1) qPCR quantification of T CD8 and B cells genes, and (2) measurement of T, B and NK cells proportions by flow cytometry.

Additionally, 964 differentially expressed genes (with a FC > 1.5 and FDR p-value < 0.05) were found between the two clusters. Interestingly, the immune-depressed cluster was enriched in ciliated and secretory epithelial cells gene signatures (p-value 2.68·10-10 and 1.28·10-6), but not in fibrosis or cell cycle related signatures.

Conclusions

The type of lung immune infiltrate defines two groups of IPF patients, which in turn are associated with different pathological features. This study opens a new perspective on the potential role of the immune response as a main driver of IPF heterogeneity.