The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients
Abstract
Pathogenic autoantibodies are a feature of systemic lupus erythematosus (SLE), of which 85% of patients are women. Multiple X chromosomes increase the risk for SLE, suggesting an important role for X-linked gene expression for the female sex bias. X-chromosome inactivation (XCI) regulates X-linked gene expression on the inactive X. This study examines XCI maintenance across multiple human B cell subsets from healthy individuals and SLE patients. Importantly, we found that both pediatric and adult SLE patient B cells have significant reductions with epigenetic modifications on the inactive X and aberrant X-linked gene expression. Our findings will be instrumental for future investigations of disease mechanisms underlying the female bias of SLE and abnormal autoantibody production in B cells.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 08, 2021
- Source ID
- 10.1073/pnas.2024624118
Entities
People
- Bam Dev Paneru
- James J. Knox
- Jane H Buckner
- Michael P Cancro
- Montserrat C Anguera
- Sarah C Pyfrom
- Sylvia Posso
Organizations
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- National Institute of Allergy and Infectious Diseases
- United States Department of Defense
- University of Pennsylvania
- Virginia Mason Medical Center