Mendelian randomization reveals clonal hematopoiesis drives T cell dysregulation in immune remodeling, indicating implications for graft-versus-host disease.
Key Points
This research aims to explore how clonal hematopoiesis influences immune system dynamics and contributes to graft-versus-host disease risk.
Utilized mendelian randomization analyses to assess causal relationships between clonal hematopoiesis and various immune traits.
Analyzed genomic data from the UK Biobank and Sardinian cohort to test 731 immune traits using MR-PRESSO and weighted mode methods.
Conducted single-cell RNA sequencing on bone marrow samples to evaluate immune cell profile changes in individuals with clonal hematopoiesis mutations.
Clonal hematopoiesis was causally associated with increased counts of hematopoietic stem and progenitor cells and monocytes.
Activated regulatory T cells showed significantly reduced frequencies, indicating impaired immune regulation and potential contribution to graft-versus-host disease.
Changes in B cell subpopulations were observed, including increased CD25 expression and reduced immature B cells, suggesting chronic activation.