Approved research

Clonal hematopoiesis and inflammatory diseases

Lay summary

Chronic inflammation is a unifying mechanism behind many aging-associated diseases. Autoimmune diseases such as rheumatoid arthritis (RA) are caused by abnormal immune activation and inflammation, affecting 5% of the population. In contrast, gout is caused by deposition of monosodium urate crystals into joints, resulting in inflammation, joint pain, and functional impairment. Clonal hematopoiesis (CH) refers to competitive growth advantage of a mutated bone marrow hematopoietic stem cell clone in individuals without a diagnosis of an overt hematologic malignancy. CH is common in older individuals and is associated with shorter life expectancy as well as increased cardiovascular disease risk due to enhanced proinflammatory signaling. The convergent inflammatory phenotype warrants studies to understand the clinical connection between CH and inflammation. We hypothesize that CH is common in patients with inflammatory diseases and that CH is associated with higher inflammatory activity in these diseases. In this UKBB project, we will leverage CHIP information from whole exome sequencing and mCA information from SNP arrays to evaluate their association with inflammatory diseases using multivariable models. We will also perform Mendelian randomization to understand whether germline risk factors of inflammatory diseases are also associated with CH risk. The expected project duration is until 2026. Understanding how clonal hematopoiesis contributes to inflammation can elucidate the pathogenesis of inflammatory diseases and can lead to novel therapeutic strategies in future, such as inhibition of the CH clones.