Clonal hematopoiesis is associated with progression of idiopathic pulmonary fibrosis

Idiopathic Pulmonary Fibrosis (IPF) is a progressive, age-associated, male-predominant fatal lung disease with heterogeneous trajectories: some patients remain stable, others deteriorate rapidly. A decline in force vital capacity (FVC)>10% is a key marker of progression. Clonal hematopoiesis (CH), defined by somatic blood cell clones at variant allele frequency (VAF)≥2%, is likewise age-related and linked to cardiovascular, pulmonary, and overall mortality risks. Given shared risk factors, we investigated the prevalence and prognostic value of CH in IPF. Whole blood for gDNA extraction was obtained after written informed consent from 97 IPF patients from the CPC-M bioArchive (Munich, Germany). ​ IPF and disease progression were diagnosed according with ATS and ERS criteria. DNA was sequenced for 13 common CH genes ( ASXL1, CALR, CBL, DNMT3A, JAK2, MPL, PPM1D, SF3B1, SRSF2, TET2, TP53, U2AF2, ZRSR2 ). Mutation and variant calling analyses were done by the Munich Leukemia Laboratory (MLL, Munich, Germany). High-impact CH mutations were defined as those predicted to disrupt the structure and/or functionality of the resulting protein, such as frameshift and stop gain alterations. CH mutations occurred in 38% of patients (median VAF 5.8%). Progressors were significantly more likely to harbor CH (53% vs. 23%, p