Clonal hemotopoiesis is the emergence of patterns of potentially problematic mutations occurring in hematopoietic stem cells that then spread over time throughout the immune system, as these stem cells are the source of all immune cells. It is the most well studied form of the somatic mosaicism that occurs in all tissues, the spread of mutations originating in stem cell populations, with some correlational evidence for it to contribute to the development of other age-related conditions. Here researchers note that clonal hematopoiesis associates with idiopathic pulmonary fibrosis, an age related condition with causes that are poorly understood. The immune system is clearly important to health, but equally the research community is some way from fully understanding how exactly disruptive mutations cause downstream problems in tissues.
Clonal hematopoiesis (CH), defined as expanded somatic blood cell clones in persons without other hematological abnormalities, is also age related. CH at variant allele frequencies (VAF) ≥2% is associated with greater risk of chronic diseases, such as coronary heart disease or chronic obstructive pulmonary disease (COPD). Commonly mutated genes (e.g., DNMT3A and TET2) epigenetically control gene expression and are important regulators of disease-related immune responses. Given these shared risk factors, we hypothesized that incidence of CH is associated with idiopathic pulmonary fibrosis (IPF) progression.
DNA was extracted from whole blood after written informed consent was obtained from 123 patients with IPF. Clinical data, available at sampling and within 12 months after blood collection, was used to assign progression (n = 89) as follows: (a) ≥10% absolute forced vital capacity (FVC) 12-month decline alone; (b) ≥5% absolute FVC 12-month decline and radiologic progression; or © 12-month radiologic progression alone. CH-defining somatic mutations were analyzed with a targeted sequencing panel (ASXL1, CALR, CBL, DNMT3A, JAK2, MPL, PPM1D, SF3B1, SRSF2, TET2, TP53, U2AF2, and ZRSR2).
CH mutations were present in 38% of patients with IPF (overall median VAF = 6.2%). Significantly more CH-mutated patients were characterized as rapid progressors (53% vs. 25%) and had a greater 12-month loss in FVC compared with those without CH (280 vs. 90 mL).
Link: https://doi.org/10.1172/jci.insight.198458
View the full article at FightAging
