Genetic and Epigenetic Dysregulation of CR1 is Associated with Catastrophic Antiphospholipid Syndrome (CAPS).

ABSTRACT:

Objective

Catastrophic antiphospholipid syndrome (CAPS), characterized by widespread thrombosis and multi-organ failure, is associated with high morbidity and mortality. We previously established complement activation as a pathogenic driver of CAPS and identified rare germline variants in complement-regulatory genes including Complement Receptor 1 (CR1) in 50% of CAPS.

Methods

We quantified CR1 expression by flow cytometry across hematopoietic cell types. CRISPR/Cas9 genome editing of TF-1 (erythroleukemia) cells was performed to generate CR1 "knock-out" and "knock-in" lines with patient-specific CR1 variants. Multiomics analysis was performed to investigate the role of methylation in CR1 expression in patients with reduced CR1 expression. Functional imp

SUBMITTER: Ranjan N 

PROVIDER: S-EPMC12083581 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature